crossing96/oncoscreening huggingface dataset:
Jagged2 progressively increased expression from Stage I to III of Bladder Cancer and Melatonin-mediated downregulation of Notch/Jagged2 suppresses the Bladder Tumorigenesis via inhibiting PI3K/AKT/mTOR/MMPs signaling.	Background: This study assessed the expression of Jagged2 in human bladder cancer (BC) tested the hypothesis that melatonin (Mel) inhibited the tumorigenesis of BC cells mainly through downregulating the Notch/Jagged2 and PI3K/AKT/mTOR/MMPs((2&9)) signaling pathways. Methods and Results: Tissue array from BC patients showed that the gene and protein expressions of JAG2/Jagged2 were significantly upregulated from T1 to T3 (primary tumor size) and from stage I to III (all p<0.001). In vitro study showed that in BC cell line of UMUC3, the cellular and protein expressions of Jagged2 were significantly attenuated in Mel-treated UMUC3 and further attenuated in UMUC3 shRNA silenced Notch/JAG2 (UMUC3(KD)) than in UMUC3 only (all p<0.0001). The protein expressions of Notch/Jagged2/MMPs((2&9))/PI3K/p-AKT/mTOR/p53/ratio of LC3BII/LC3B-I were significantly progressively reduced from UMUC3 to UMUC3+Mel/1.0mM, further to UMUC3+Mel/2.0mM and furthermore to UMUC3(KD) (all p<0.0001). The cell proliferation/invasion/colony formation/healing-process were significantly inhibited in Mel-treated/2.0mM UMUC3 and further significantly inhibited in UMUC3(KD) regardless of Mel treatment as compared with UMUC3 only (all p<0.0001). By day 28 after UMUC3 implanted into nude mouse back, the BC weight/volume were significantly reduced in UMUC3+Mel (100 mg/kg/day) and furthermore reduced in UMUC3(KD) (all p<0.0001) as compared with UMUC3 only (all p<0.0001). The cellular (MMPs((2&9))/Notch/Jagged2) and protein (Notch/Jagged2/PI3K/p-AKT/mTOR/MMPs((2&9))) exhibited a similar trend, whereas the PTEN protein level exhibited an opposite pattern of PI3K among three groups (all p<0.0001). Conclusion: Notch/Jagged-PI3K/p-AKT/mTOR/MMPs is one essential signaling pathway for BC survival, proliferation and invasion that were remarkably suppressed by Mel treatment.	bladder
Impact of noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy on bladder-sparing strategy in patients with muscle-invasive bladder cancer.	OBJECTIVE: To identify the optimal selection criteria for bladder sparing strategy with transurethral resection of bladder tumor (TURBT) and systemic chemotherapy in patients with muscle-invasive bladder cancer (MIBC). METHODS: We conducted a retrospective cohort study in 71 patients with MIBC (T2-4aN0M0) who desire to bladder preservation received neoadjuvant chemotherapy (NAC) after maximal TURBT, followed by clinical restaging and second-TURBT. Fifty-eight of 71 patients with no residual tumor on the second-TURBT were placed on conservative management for bladder sparing (BS). Noninvasive down-staging (NID) was defined as cT0/Ta/Tis/T1N0 at first-TURBT after NAC and no residual tumor on second-TURBT. Overall survival (OS) and cystectomy-free survival (CFS) were assessed according to the response of NAC in the BS group by using Kaplan-Meier methods. Cox proportional hazards regression model was used to identify independent variables predicting OS. RESULTS: At a median follow-up of 40 months 5-year OS and CFS in patients with NID and non-NID were 89.1% versus 20.8% and 84.8% versus 16.7%, respectively. Multivariate analysis showed that the ≥3 cycles of NAC (hazard ratio [HR] 0.14, 95% confidential index [CI] 0.03-0.7; P = 0.017) and achievement of NID (HR 0.11, 95% CI 0.03-0.46, P = 0.002) favorably associated with OS. CONCLUSIONS: Patients who achieved NID might be optimal candidates for the bladder sparing strategy with maximum TURBT plus NAC followed by second-TURBT.	bladder
The Remaining Ipsilateral Ureteral Orifice Provokes Intravesical Tumor Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multicenter Study With a Mid-Term Follow-Up.	OBJECTIVES: To investigate the impact of the remnant ureteral orifice (RUO) on the prognosis of upper tract urothelial carcinoma (UTUC), because the presence of an ipsilateral intact ureteral orifice is not an uncommon finding during follow-up cystoscopy despite the clinical relevance of bladder cuffing during radical nephroureterectomy (RNU) for the management of UTUC. METHODS: The records of patients who underwent RNU in all tertiary hospitals in Daegu province (2011-2018) were retrospectively reviewed. Subjects were allocated to RUO or non-RUO groups. Cox proportional hazard models were used to identify variables. The primary endpoint was a 5-year intravesical recurrence-free survival (RFS). RESULTS: Of the 164 patients enrolled, 45 (27.4%) had an RUO by postoperative cystoscopy. The characteristics of the RUO and non-RUO groups were similar. During mean follow-up of 76.4 months (range: 69.5-83.4), 21 (46.7%) subjects in the RUO group and 25 (21.0%) in the non-RUO group experienced intravesical recurrence (P = .001). Among them, 3 (6.7%) and 14 (8.5%) developed distant metastasis (P = .339), and 3 (6.7%) and 9 (7.6%) succumbed to UTUC (P = .844), respectively. The 5-year RFS was lower in the RUO group than in the non-RUO counterpart (45.6% vs 77.8%, P = .003). Multivariate analysis showed lymphovascular invasion (hazard ratio [HR] = 3.593, P = .002), lymph nodal involvement (HR = 2.336, P = .038), and the presence of RUO (HR = 2.058, P = .026) predicted 5-year RFS. CONCLUSION: The presence of RUO after RNU was found to be significantly associated with intravesical tumor recurrence, and this finding emphasizes the quality of bladder cuffing during RNU, which could be assessed by complete removal of the natural orifice.	bladder
Bladder Cancer: A Comparison Between Non-urothelial Variant Histology and Urothelial Carcinoma Across All Stages and Treatment Modalities.	BACKGROUND: The purpose of this study was to evaluate stage at presentation, treatment rates, and cancer-specific mortality (CSM) of non-urothelial variant histology (VH) bladder cancer (BCa) relative to urothelial carcinoma of the urinary bladder (UCUB). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), patients with VH BCa and UCUB were identified. Stage at presentation and treatment rates, as well as multivariably adjusted and matched CSM rates according to TNM stage within each histologic subtype, were reported. RESULTS: Of all 222,435 eligible patients with BCa, 11,147 (5.0%) harbored VH. Among those, squamous cell carcinoma accounted for 3666 (1.6%) patients, adenocarcinoma for 1862 (0.8%), neuroendocrine carcinoma for 1857 (0.8%), and other VH BCa for 3762 (1.7%) of the study cohort. Patients with VH BCa showed invariably more advanced TNM stage at presentation compared with patients with UCUB. Treatment rates according to TNM stages showed similar distribution of cystectomy rates in VH BCa and UCUB. However, important differences in the distribution of radiotherapy and chemotherapy rates existed within VH BCa and in comparison with UCUB. Furthermore, even after multivariable adjustment and matching with UCUB, squamous cell carcinoma exhibited higher CSM (hazard ratios, 1.43-1.95; all P < .01) across all stages. All other VH predominantly exhibited higher CSM than UCUB in either non-muscle-invasive or muscle-invasive nonmetastatic stages. CONCLUSION: TNM stage at diagnosis is invariably more advanced in all patients with VH BCa versus patients with UCUB. Of all VH BCa, in multivariably adjusted stage for stage analyses, squamous cell carcinoma appears to have the worst natural history. All other VH subgroups exhibited more aggressive natural history than UCUB in nonmetastatic stages only.	bladder
Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells.	Histone demethylase KDM7A regulates many biological processes, including differentiation, development, and the growth of several cancer cells. Here, we have focused on the role of KDM7A in bladder cancer cells, especially under drug-resistant conditions. When the KDM7A gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown in the bladder cancer cells repressed the activity of androgen receptor (AR) through epigenetic regulation. When we developed a cisplatin-resistant bladder cancer cell line, we found that AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells, showed decreased cell proliferation. In the mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of the bladder tumor. We also observed the upregulation of KDM7A expression in patients with bladder cancer. The findings suggest that histone demethylase KDM7A mediates the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in patients with cisplatin-resistant bladder cancer.	bladder
Immunotherapy and associated immune-related adverse events at a large UK centre: a mixed methods study.	BACKGROUND: The development and rapid uptake of immune checkpoint inhibitors (CPI) has changed the outlook for patients with cancer. However, CPIs have different adverse event (AE) profiles to other systemic therapies, and prompt AE management is essential to assure optimal outcomes. In order to understand what and when adverse events are experienced, reported and managed during CPI treatment, a mixed methods study was conducted, including a case note review of patients who were receiving immunotherapy and semi-structured interviews with patients to understand their experience, management and reporting of AEs after receiving immune CPI treatment. METHODS: This mixed methods study was conducted at a large cancer hospital in the United Kingdom. A case note review identified how and where patients reported AEs. Data relating to patients with lung, bladder, prostate and head & neck cancers who received CPI treatment between 01/04/2015 and 31/07/2018 were extracted from e-prescribing databases and clinical data were included for analysis at a single time point (31 July 2018). Semi-structured interviews were conducted with patients receiving CPI treatment, exploring experience of AEs and reasons for delays in AE reporting and management. RESULTS: Sixty-two patients were included in the case note review, with 78 AEs being experienced by 36 patients (58%), including one patient experiencing 10 AEs. Serious AEs were experienced by 12 patients (19%) and ten AEs (17%) required oral steroids as treatment. The majority of AEs were reported to clinicians prior to further dosing, although milder AEs were often not addressed until subsequent clinic appointments. Interviews with 13 patients yielded major themes: variability, causality, decision making and impact. CONCLUSION: Most CPI-associated AEs are manageable if reported and treated promptly. Both the case note review and interviews found that reporting of non-serious AEs is often left until routine clinic visits, despite impacting patient experience, leaving the opportunity for AEs to be left unreported and implying a potential benefit for real time monitoring. Our study highlights a need to provide patients with reminders around AEs and their timely reporting even when apparently innocuous; patients must understand that AEs can occur at any cycle and even following treatment completion.	bladder
Inflammatory Myofibroblastic Tumor of the Urinary Bladder and Ureter in Children: Experience of a Tertiary Referral Center.	PURPOSE: To present the clinicopathological characteristics and outcome of children with bladder and ureteral inflammatory myofibroblastic tumors (IMTs) in our center. METHODS: We reviewed the medical records of patients with bladder and ureteral IMTs from 2010 to 2018. We recorded patients' demographic data, presentation, hemoglobin level, presence of hydronephrosis, tumor size, treatment, and outcomes. RESULTS: Eight patients with bladder IMTs and 3 with ureteral IMTs were treated at our center during this period. The mean age was 7.1 years. Four patients presented with anemia at diagnosis with the mean hemoglobin level 84.5 g/L. Among patients with bladder IMTs, 5 were male and 3 were female. The most common symptom was lower urinary symptoms in 6 patients, followed by hematuria in 4 patients. 2 patients had complications of hydronephrosis and hydroureter. Among patients with ureteral IMTs, 2 were male and one was female. The most common symptom was abdominal pain, and 3 patients presented with upper urinary tract dilation. All patients underwent surgery. A total of 81.8% were positive for anaplastic lymphoma kinase. Cytokeratin (CK) expression was present in all patients with bladder IMTs, while it was negative in 2 patients with ureteral IMTs. During mean follow-up of 43.4 months, all patients survived event-free. CONCLUSION: The presence of hydronephrosis and hydroureter is rare in patients with bladder IMTs. Anemia caused by hematuria should be raised the index of suspicion for IMTs. Children with bladder and ureteral IMTs had excellent prognosis. The expression pattern of CK varied between bladder and ureteral IMTs.	bladder
[Individual control of urine volume to improve stability of bladder volume in radiotherapy of urinary tumor].	OBJECTIVE: To explore the training mode of individual urine volume control, to take indi-vidual expected urine volume as the goal of bladder control in patients with urinary system tumors, and to improve the accuracy of bladder control during radiotherapy by active training of bladder receptivity. METHODS: Twenty-five patients of urinary system tumors were enrolled from May 2019 to September 2019, of whom, 21 patients had prostate cancer, and 4 had bladder cancer. Training of bladder filling started before CT simulation. The patients were required to take the individual bladder filling as the training goal, and the optimal bladder volume range was suggested to be 200－400 mL. After 2－4 weeks of training, the prescribed volume of the bladder was determined according to the patient's bladder receptivity. The volume of the bladder was measured by images of plain CT and images 8-minutes after intravenous contrast injection. The patient's bladder volume was measured using BladderScan before treatment. CBCT (Cone-beam CT) was performed, and bladder volume was measured before treatment. The bladder volume was measured again using BladderScan after treatment. RESULTS: The mean bladder volume of simulation (V(CT01)) was (262±130) mL, ranging from 78 mL to 505 mL. The mean self-evaluation bladder volume before radiotherapy (V(EVA01)) was (238±107) mL, ranging from 100 mL to 400 mL. The mean BladderScan measured volume before radiotherapy (V(BVI01)) was (253±123) mL, ranging from 60 mL to 476 mL. The mean cone-beam CT measured volume before radiotherapy (V(CBCT)) was (270±120) mL, ranging from 104 mL to 513 mL. There was a correlation between V(EVA01) and V(BVI01), V(CT01) and V(BVI01), V(CT01,) and V(BVI01), and there was no significant difference in paired t-test. There was a correlation between differences of self-evaluation bladder volume before radiotherapy(V(EVA01)) and simulation CT (V(CT01)) and differences of self-evaluation bladder volume before radiotherapy (V(EVA01)) and cone-beam CT (V(CBCT)), and there was no significant difference in paired samples by t-test. CONCLUSION: During radiotherapy for urinary system tumors, such as prostate cancer and bladder cancer, with the assistance of BladderScan, the patients could try to hold their urine moderately according to their conditions, and individualized bladder prescription may be beneficial to achieve stable bladder volume during radiotherapy.	bladder
Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.	BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.	bladder
Advanced colonic cancer with clinically suspected bladder invasion: Outcomes and prognosis from a multicentric study of 117 patients from the FRENCH research group.	BACKGROUND: Bladder invasion by colon cancer is rare; however, its management is still controversial. Our objective was to report outcomes and identify risk factors for local recurrence in colon cancer with clinically suspected bladder invasion. METHODS: We conducted a retrospective study in 23 centers in France. All patients who underwent colon surgery with bladder resection (2010-2017) were included. Metastatic and recurrent colon cancers were excluded. RESULTS: One hundred and seventeen patients (men = 73) were included. Partial cystectomy occurred in 108 patients (92.3%), with a total cystectomy occurring in 9 patients (7.7%). Neoadjuvant treatment was given to 31 patients (26.5%). Major morbidity was 20.5%. R0 resection rates were 87.2%. Histologically confirmed bladder invasion was present in 47%. Thirty-four patients were pN+, while 60 patients (51.3%) received adjuvant chemotherapy. Mean follow-up was 33.8 months. Three-year overall survival and disease-free survival were 82.9% and 59.5%. Rates of local recurrence and distant recurrence were 14.5% and 18.8%, respectively; the local recurrences (11/17; 65%) were in the bladder, while 4 of these patients had a bladder recurrence despite not having histologically confirmed bladder invasion at the index surgery. The rate of bladder recurrence after histologic bladder invasion was 13% (7/55), while the rate of bladder recurrence without primary bladder invasion was 7% (4/62) (P = .343). Neoadjuvant therapy, type of cystectomy, and adjuvant therapy did not influence local recurrence (P > .445 each). R1 bladder resections, when compared with a R0 bladder resections, were associated with an increased rate of local recurrence (63% vs 10%; P < .0001). CONCLUSION: Clinically suspected bladder invasion increases local recurrence even in the absence of histologically confirmed bladder invasion. Only complete resections with R0 margins decrease local recurrence. Careful, detailed postoperative surveillance is required, even without pathologic bladder invasion.	bladder
Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer.	Reactive Oxygen Species Modulator 1 (ROMO1) plays a pivotal role in the regulation of mitochondrial structure integrity, and the production of reactive oxygen species (ROS). Increased ROMO1 expression was reported in various cancer cell lines; however, the possible association between ROMO1 expression and bladder cancer was not well studied. The present study aimed to investigate the rate of ROMO1 expression and the correlation of oxidative stress with the development of bladder cancer. In this study, a total of 35 cancerous and healthy adjacent tissues were examined using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the gene expression of ROMO1. Also, we evaluated the serum level of ROMO1 and Total Antioxidant Capacity (TAC), as well as Total Oxidant Status (TOS) in patients with bladder cancer along with age- and sex-matched healthy individuals. The ROMO1 gene was significantly higher in cancerous tissues than that of adjacent healthy tissues. Also, the serum levels of ROMO1, TAC, TOS, and Oxidative Stress Index (OSI) were increased in patients with bladder cancer compared with healthy subjects. It can be concluded that the overexpression of the ROMO1 gene is associated with advanced grades of bladder cancer as well as an increase in oxidative stress conditions. Our findings also suggest that the serum level of ROMO1 might be a promising tumor marker for bladder cancer.	bladder
Therapeutic Applications of Curcumin and its Novel Formulations in the Treatment of Bladder Cancer: A Review of Current Evidence.	Bladder cancer, a life-threatening serious disease, is responsible for thousands of cancer-associated deaths worldwide. Similar to other malignancies, standard treatments of bladder cancer, such as Chemoradiotherapy, are not efficient enough in the affected patients. It means that, according to recent reports in the case of life quality as well as the survival time of bladder cancer patients, there is a critical requirement for exploring effective treatments. Recently, numerous investigations have been carried out to search for appropriate complementary treatments or adjuvants for bladder cancer therapy. Curcumin, a phenolic component with a wide spectrum of biological activities, has recently been introduced as a potential anti-cancer agent. It has been shown that this agent exerts its therapeutic effects via targeting a wide range of cellular and molecular pathways involved in bladder cancer. Herein, the current data on curcumin therapy for bladder cancer are summarized.	bladder